The objectivesof this proposed research are: (a) To investigate the relationship between the levels of lipoprotein-cholestrol and those of dehydroisoandrosterone sulfate (DS) an 16a-OHdehydroisoandrosterone sulfate (16alpha-OHDS) in umbilical cord plasma of normal newborns of normal mothers and in newborns whose mothers had hypertension, pregnancy-induced hypertension, diabetes mellitus and other malades that may impose high-risk on the fetus. (b) To investigate the nature of the apparent paradox that in pregnancies in which the fetus is believed to be "stressed", the levels of estriol in the maternal compartment are low. (c) To evaluate the role of lipoproteins in the fetal circulation, especially low-density lipoprotein (LDL), in the regulation of fetal adrenal steroidogenesis. (d) To ascertain whether the level of LDL-cholesterol in fetal plasma is a sensitive index of fetal adrenal function. (e) To investigate the biosynthesis and metabolism of lipoproteins in the fetal or fetoplacental compartment. We suggest that circulating LDL-cholesterol is the preferred substrate for fetal adrenal steroidogenesis and we hypothesize that the rapid utilization of LDL by the fetal adrenal accounts for the low levels of this lipoprotein in umbilical cord plasma. We also speculate that fetal "stress", i.e., hypoxia, is accompaaied by decreased fetal pituitary ACTH secretion which leads to decreased adrenal DS secretion, decreased 16a-OHDS formation and thence a fall in the rate of estriol synthesis in the placenta. As a consequence of decreased adrenal function, LDL-cholesterol levels in the fetal circulation rise. We propose to test these hypotheses in a systematic manner in order to gain insight into the factors that control adrenal function in the human fetus and to gain a better understanding of the pathophysiology of endocrine function in the fetus believed to be at high-risk.